V-Acetylcysteine

The recent work by Winterbourn and Metodiewa [211] demonstrated that the above values for the rate constant of reaction of DHLA with superoxide might be overestimated. These authors studied the reactions of superoxide with several thiols, glutathione, cysteine, cysteamine, penicillamine, /V-acetylcysteine, dithiothreitol, and captopril and found that thiols reacted with superoxide by a chain mechanism with the regeneration of superoxide. They suggested that the rate constants for the reactions of thiols with superoxide could not be more than 103 ImoN1 s-1. 

Wegener, T., B. Sandhagen, K.W. Chan, and T. Saldeen. 1988. V-acetylcysteine in paraquat toxicity toxicological and histological evaluation in rats. Uppsala Jour. Med. Sci. 93 81-89. 

The chemical and toxicologic characterization of the electrophilic nature of the reactive acetaminophen metabolite has led to the development of effective antidotes—cysteamine and /V-acetylcysteine. Administration of /V-acetylcysteine (the safer... 

Banner W, Koch M, Capin M, et al. 1986. Experimental chelation therapy in chromium, lead, and boron intoxication with V-acetylcysteine and other compounds. Toxicol Appl Pharmacol 83 142-147. 

A report on the biomedical application of activated carbon adsorption [600] is also revealing. The authors analyzed the uptakes of an aromatic compound, acetaminophen (active ingredient in Tylenol, pKj = 9.5), and an aliphatic one, (V-acetylcysteine (which provides a protective effect against acetaminophen overdose pKa = 3.3), under both gastric (pH = 1.2) and intestinal (pH = 7.0) conditions. Their results are reproduced in Table 24. 

Weber, G. L., Steenwyk, R. C., Nelson, S. D., Pearson, P. G. Identification of V-acetylcysteine conjugates of l,2-dibromo-3-chloropropane evidence for cytochrome P450 and glutathione mediated bioactivation pathways. Chem. Res. Toxicol. 1995, 8, 560—573. 

Oda, T., Iwaoka, J., Komatsu, N. and Muramatsu, T. (1999) Involvement of /V-acetylcysteine-sensitive pathways in ricin-induced apoptotic cell death in U937 cells. Biosci Biotechnol Biochem, 63, 341-348. 

The final sulfur mustard urinary biomarker to be discussed is also a reaction product of sulfur mustard with glutathione 1,1 -sulfonyl-bis-[2-S-(V-acetylcystein T)ethane. Using solid-phase extraction for sample cleanup and analyte concentration followed by analysis with negative ion electrospray LC-MS-MS, Read and Black (2004b) were able to achieve detection limits of 0.5-1.0 ng/mL. Methods for the analysis of urine samples for sulfur mustard verification are summarized in Table 19.5. 

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